The role of the normal flora in preventing respiratory infections and antibiotic resistance spread.

Streptococcus pneumoniae is a major colonizer of the respiratory tract and a leading cause of severe morbidity and mortality worldwide and infections with antibiotic resistant organisms are increasing.

Asymptomatic colonization is accomplished through the intricate balance between pathogens, the host response, and the resident microbiota (normal flora) and provides a niche for acquisition and spread of antimicrobial resistance.

Changes in the host environment due to virus infection and/or changes in the microbiota composition can trigger pneumococci to transition from asymptomatic colonization to disease.The overall aim of our studies is to characterize the mechanisms involved in homeostasis and dysregulation in the respiratory tract and how that influences colonization, spread of antibiotic resistance (Aim 1), and transition to disease using in vitro models (Aim 2) and in animal studies and patient samples in vivo (Aim 3)Our studies will provide novel information about pneumococcal colonization, antibiotic resistance acquisition, and transition to infection and allow us to both identify bacterial and host molecules involved in these processes that can act as targets for future therapeutic and preventive intervention, as well as determine the role of species from the respiratory microbiota as potential probiotics.